Anesthetics significantly impact animal models of experimental stroke. Preliminary studies have shown that peri-infarct depolarizations (PIDs), likely effectors of infarct expansion in both rats and humans, are particularly sensitive to confounding effects of isoflurane anesthesia. Proposed studies will effectively eliminate such confounds in experimental stroke, and achieve a reliable assessment of stroke pathophysiology in the awake state. Studies will proceed in three staged aims: 1) define a recovery interval after initial isoflurane exposure that is sufficiently long to avoid its confounding impact on PIDs;2) use chronically implanted electrode arrays to characterize PID incidence during recovery from naive anesthesia exposure following MCA occlusion, replicating conditions of conventional stroke modeling;3) implement and evaluate an MCA occlusion model in awake rats, thereby eliminating both acute and chronic confounds of anesthesia exposure. Results of these experiments will permit more direct comparison of animal studies with evolving observations in patients, and potentially lead to improved methods for translational stroke research. PUBLIC HEALTH RELEVANCE: Problems remain in effectively translating experimental results to benefits in clinical stroke, in part reflecting the impact of anesthesia in animal models. Proposed studies will effectively eliminate such confounds in experimental stroke, and achieve the first reliable assessment of acute stroke pathophysiology in the awake state. This will permit more direct comparison of animal studies with observations in patients.